The C57Bl/6 mouse serves as a suitable model of human skeletal muscle mitochondrial function

Abstract

It is debatable whether differences in mitochondrial function exist across skeletal muscle types and whether mouse skeletal muscle mitochondrial function can serve as a valid model for human skeletal muscle mitochondrial function. The aims of this study were to compare and contrast three different mouse skeletal muscles and to identify the mouse muscle that most closely resembles human skeletal muscle respiratory capacity and control. Mouse quadriceps (QUAD(M)), soleus (SOL(M)) and gastrocnemius (GAST(M)) skeletal muscles were obtained from 8- to 10-week-old healthy mice (n = 8), representing mixed, oxidative and glycolytic muscle, respectively. Skeletal muscle samples were also collected from young, active, healthy human subjects (n = 8) from the vastis lateralis (QUAD(H)). High-resolution respirometry was used to examine mitochondrial function in all skeletal muscle samples, and mitochondrial content was quantified with citrate synthase activity. Mass-specific respiration was higher across all respiratory states in SOL(M) versus both GAST(M) and QUAD(H) (P < 0.01). When controlling for mitochondrial content, however, SOL(M) respiration was lower than GAST(M) and QUAD(H) (P < 0.05 and P < 0.01, respectively). When comparing respiratory capacity between mouse and human muscle, QUAD(M) exhibited only one different respiratory state when compared with QUAD(H). These results demonstrate that qualitative differences in mitochondrial function exist between different mouse skeletal muscles types when respiratory capacity is normalized to mitochondrial content, and that skeletal muscle respiratory capacity in young, healthy QUAD(M) does correspond well with that of young, healthy QUAD(H).